This research project proposes to investigate the structure-activity rules for the biologic effects of polychlorinated biphenyls (PCBs) on the hepatic system. It has been proposed that there is a correlation which suggests that the toxic halogenated aromatic hydrocarbons are those which elicit biologic effects such as binding to a cytosolic receptor protein and induce hepatic microsomal aryl hydrocarbon hydroxylase (AHH) activity. The project will use genetically inbred mouse strains and a series of PCBV congeners which have been previously synthesized and studied in immature male rats. The biologic effects of the structurally diverse PCBs will be determined by measuring hepatic microsomal benzo(a)pyrene hydroxylase, dimethylaminoantipyrine N-demethylase, 4-chlorobiphenyl hydroxylase, NADPH cytochrome capa reductase, styrene epoxide hydratase and benzo(a)pyrene-4,5-oxide hydratase enzyme activities, the cytoxhrome b5 content, the relative peak intensities of the reduced microsomal cytochrome P-450:CO and ethylisocyanide binding difference spectra and the SDS electrophoretic patterns of the microsomal proteins. The biologic studies will also include HPLC analysis of benzo(a)pyrene metabolites, the binding of PCB congeners to the cytosol receptor protein and evaluating the possible correlation between binding potency and AHH induction activity of the PCB congeners. The toxicity of the PCBs will be determined by their effects on splenic and thymic involution in the genetically responsive mouse strains and their effects on several target organs. The animals at the high dose levels at PCBs will be necropsied within 2 hours after death and the flowing tissues will be fixed in l0% phoshpate-buffered formalin (pH 7.4) and submitted for slide preparation and examination by light microscopy; brain, liver, kidney, heart, thymus, spleen, adrenal glands, lungs, thyroid and pancreas.